A Review of the Mechanism of Action of Cyclosporine A: The Role of Cyclosporine A in Dry Eye Disease and Recent Formulation Developments

Laura M Periman,1 Francis S Mah,2 Paul M Karpecki3 1Periman Eye Institute, Seattle, WA, USA; 2Scripps Health, La Jolla, CA, USA; 3Kentucky Eye Institute, Lexington, KY, USACorrespondence: Laura M PerimanPeriman Eye Institute, Seattle, WA, USAEmail dryeyemaster@gmail.comAbstract: Dry eye disease (DED...

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Autores principales:	Periman LM, Mah FS, Karpecki PM
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	dry eye disease cyclosporine a emulsion otx-101 keratoconjunctivitis sicca Ophthalmology RE1-994
Acceso en línea:	https://doaj.org/article/fae4aabda76641bc982bd5717d067a8c
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spelling	oai:doaj.org-article:fae4aabda76641bc982bd5717d067a8c2021-12-02T14:59:19ZA Review of the Mechanism of Action of Cyclosporine A: The Role of Cyclosporine A in Dry Eye Disease and Recent Formulation Developments1177-5483https://doaj.org/article/fae4aabda76641bc982bd5717d067a8c2020-12-01T00:00:00Zhttps://www.dovepress.com/a-review-of-the-mechanism-of-action-of-cyclosporine-a-the-role-of-cycl-peer-reviewed-article-OPTHhttps://doaj.org/toc/1177-5483Laura M Periman,1 Francis S Mah,2 Paul M Karpecki3 1Periman Eye Institute, Seattle, WA, USA; 2Scripps Health, La Jolla, CA, USA; 3Kentucky Eye Institute, Lexington, KY, USACorrespondence: Laura M PerimanPeriman Eye Institute, Seattle, WA, USAEmail dryeyemaster@gmail.comAbstract: Dry eye disease (DED) is a multifactorial disease of the ocular surface and tear film that has gained awareness as a public health problem. Characteristics of DED include tear film instability, hyperosmolarity, and ocular surface inflammation, which can occur independently or may be a sequela of numerous ocular diseases, ocular surgery or contact lens wear. Much has been learned about the impact of the disease to help affected individuals who report symptoms of poor vision, pain, and tearing. Recently, new research highlights the importance of the role of ocular surface inflammation and damage in DED—leading to a vicious cycle of inflammation as well as loss of tear film homeostasis. DED immunopathophysiology is characterized by four stages: initiation, amplification, recruitment, and re-initiation. Cyclosporine is proven to be a valuable ophthalmic therapeutic for DED through its immunomodulatory actions and regulation of the adaptive immune response. Cyclosporine mechanism of action is well described in the published literature and the myriad of benefits in all four stages lend a broad-based immunomodulatory function particularly suitable for addressing DED. Furthermore, cyclosporine has unique goblet cell density improvement capabilities as well as anti-apoptotic properties. Topical formulations of cyclosporine are centered around addressing the highly lipophilic nature of the molecule. The poor aqueous solubility of cyclosporine traditionally presented technical challenges in drug delivery to the ocular surface. Newer formulations such as cationic emulsions and nanomicellar aqueous solutions address formulation, tissue concentration, and drug delivery challenges.Keywords: dry eye disease, cyclosporine A, emulsion, OTX-101, keratoconjunctivitis siccaPeriman LMMah FSKarpecki PMDove Medical Pressarticledry eye diseasecyclosporine aemulsionotx-101keratoconjunctivitis siccaOphthalmologyRE1-994ENClinical Ophthalmology, Vol Volume 14, Pp 4187-4200 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	dry eye disease cyclosporine a emulsion otx-101 keratoconjunctivitis sicca Ophthalmology RE1-994
spellingShingle	dry eye disease cyclosporine a emulsion otx-101 keratoconjunctivitis sicca Ophthalmology RE1-994 Periman LM Mah FS Karpecki PM A Review of the Mechanism of Action of Cyclosporine A: The Role of Cyclosporine A in Dry Eye Disease and Recent Formulation Developments
description	Laura M Periman,1 Francis S Mah,2 Paul M Karpecki3 1Periman Eye Institute, Seattle, WA, USA; 2Scripps Health, La Jolla, CA, USA; 3Kentucky Eye Institute, Lexington, KY, USACorrespondence: Laura M PerimanPeriman Eye Institute, Seattle, WA, USAEmail dryeyemaster@gmail.comAbstract: Dry eye disease (DED) is a multifactorial disease of the ocular surface and tear film that has gained awareness as a public health problem. Characteristics of DED include tear film instability, hyperosmolarity, and ocular surface inflammation, which can occur independently or may be a sequela of numerous ocular diseases, ocular surgery or contact lens wear. Much has been learned about the impact of the disease to help affected individuals who report symptoms of poor vision, pain, and tearing. Recently, new research highlights the importance of the role of ocular surface inflammation and damage in DED—leading to a vicious cycle of inflammation as well as loss of tear film homeostasis. DED immunopathophysiology is characterized by four stages: initiation, amplification, recruitment, and re-initiation. Cyclosporine is proven to be a valuable ophthalmic therapeutic for DED through its immunomodulatory actions and regulation of the adaptive immune response. Cyclosporine mechanism of action is well described in the published literature and the myriad of benefits in all four stages lend a broad-based immunomodulatory function particularly suitable for addressing DED. Furthermore, cyclosporine has unique goblet cell density improvement capabilities as well as anti-apoptotic properties. Topical formulations of cyclosporine are centered around addressing the highly lipophilic nature of the molecule. The poor aqueous solubility of cyclosporine traditionally presented technical challenges in drug delivery to the ocular surface. Newer formulations such as cationic emulsions and nanomicellar aqueous solutions address formulation, tissue concentration, and drug delivery challenges.Keywords: dry eye disease, cyclosporine A, emulsion, OTX-101, keratoconjunctivitis sicca
format	article
author	Periman LM Mah FS Karpecki PM
author_facet	Periman LM Mah FS Karpecki PM
author_sort	Periman LM
title	A Review of the Mechanism of Action of Cyclosporine A: The Role of Cyclosporine A in Dry Eye Disease and Recent Formulation Developments
title_short	A Review of the Mechanism of Action of Cyclosporine A: The Role of Cyclosporine A in Dry Eye Disease and Recent Formulation Developments
title_full	A Review of the Mechanism of Action of Cyclosporine A: The Role of Cyclosporine A in Dry Eye Disease and Recent Formulation Developments
title_fullStr	A Review of the Mechanism of Action of Cyclosporine A: The Role of Cyclosporine A in Dry Eye Disease and Recent Formulation Developments
title_full_unstemmed	A Review of the Mechanism of Action of Cyclosporine A: The Role of Cyclosporine A in Dry Eye Disease and Recent Formulation Developments
title_sort	review of the mechanism of action of cyclosporine a: the role of cyclosporine a in dry eye disease and recent formulation developments
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/fae4aabda76641bc982bd5717d067a8c
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A Review of the Mechanism of Action of Cyclosporine A: The Role of Cyclosporine A in Dry Eye Disease and Recent Formulation Developments

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